Evaluation of commonly used ectoderm markers in iPSC trilineage differentiation.

Patient-derived induced pluripotent stem cells (iPSCs) have become a promising resource for exploring genetics of complex diseases, discovering new drugs, and advancing regenerative medicine. Increasingly, laboratories are creating their own banks of iPSCs derived from diverse donors. However, there are not yet standardized guidelines for qualifying these cell lines, i.e., distinguishing between bona fide human iPSCs, somatic cells, and imperfectly reprogrammed cells. Here, we report the establishment of a panel of 30 iPSCs from CD34+ peripheral blood mononuclear cells, of which 10 were further differentiated in vitro into all three germ layers. We characterized these different cell types with commonly used pluripotent and lineage specific markers, and showed that NES, TUBB3, and OTX2 cannot be reliably used as ectoderm differentiation markers. Our work highlights the importance of marker selection in iPSC authentication, and the need for the field to establish definitive standard assays

The Challenge of Diagnosing Atheroembolic Renal Disease

Background— Atheroembolic renal disease (AERD) is caused by showers of cholesterol crystals released by eroded atherosclerotic plaques. Embolization may occur spontaneously or after angiographic/surgical procedures. We sought to determine clinical features and prognostic factors of AERD. Methods and Results— Incident cases of AERD were enrolled at multiple sites and followed up from diagnosis until dialysis and death. Diagnosis was based on clinical suspicion, confirmed by histology or ophthalmoscopy for all spontaneous forms and for most iatrogenic cases. Cox regression was used to model time to dialysis and death as a function of baseline characteristics, AERD presentation (acute/subacute versus chronic renal function decline), and extrarenal manifestations. Three hundred fifty-four subjects were followed up for an average of 2 years. They tended to be male (83%) and elderly (60% >70 years) and to have cardiovascular diseases (90%) and abnormal renal function at baseline (83%). AERD occurred spontaneously in 23.5% of the cases. During the study, 116 patients required dialysis, and 102 died. Baseline comorbidities, ie, reduced renal function, presence of diabetes, history of heart failure, acute/subacute presentation, and gastrointestinal tract involvement, were significant predictors of event occurrence. The risk of dialysis and death was 50% lower among those receiving statins. Conclusions— Clinical features of AERD are identifiable. These make diagnosis possible in most cases. Prognosis is influenced by disease type and severity

Rituximab versus steroids and cyclophosphamide for the treatment of primary membranous nephropathy: protocol of a pilot randomised controlled trial

Introduction: Primary membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The disease may have different long-term outcomes. After 10 years of follow-up, 35%-50% of the untreated patients with persistent nephrotic syndrome may die or progress to end stage renal disease. The 2012 KDIGO (Kidney Disease Improving Global Outcomes) guidelines recommend that initial therapy should consist of alternating steroids and an alkylating agent for 6 months. Recent observational studies showed that the anti-CD20 antibody rituximab may be effective in inducing remission. We designed a pilot multicentre randomised trial to inform the design of a larger trial testing the efficacy and safety of treatment with steroids and cyclophosphamide versus rituximab in patients with primary MN and heavy proteinuria (>3.5 g/24 hours). Methods and analysis: This pilot, open-label, two-parallel-arm, randomised clinical trial will enrol 70 patients with primary MN and heavy proteinuria. Patients will be randomised in a 1:1 ratio to either the intervention arm (rituximab) or the active comparator arm (corticosteroid/alkylating-agent therapy). The study will provide estimates of the probability of complete remission of proteinuria and risk of serious side effects at 12 months to inform the design of a larger trial. We will also assess the recruitment potential of each participating centre to address study feasibility. Ethics and dissemination: The trial received ethics approval from the local ethics boards. We will publish pilot data to inform the design of a larger clinical trial. Trial registration numbers: NCT03018535; 2011-006115-59

Mobilità dei pittori e identità delle produzioni

Gli atti di questo convegno segnano l’avvio della pubblicazione di una serie di ricerche sistematiche sulla ceramica italiota condotte da un gruppo di specialisti da tempo impegnati ad evidenziare le conoscenze disponibili su questa produzione nella fase “post-Trendall”, e accomunati dalla volontà di valorizzare la ceramica figurata come documento capace di contribuire a chiarire aspetti della storia della Magna Grecia di epoca classica ed ellenistica. Partendo dal caso di studio della tomba 100 di Torre di Mare (Metaponto, Matera), i contributi si concentrano sul tema della mobilità dei pittori e del ruolo da essa giocato nella costituzione dell’identità di una produzione. La mobilità degli artigiani, non è, infatti, un tratto esclusivo della ceramica italiota, e l’attenzione riservata dagli studi più recenti alle problematiche legate alla produzione ha permesso di meglio comprendere i fenomeni che presiedono alla diffusione delle tecniche e degli stili e che contribuiscono alla nascita o alla fine delle produzioni nelle differenti regioni del mondo greco, soprattutto in relazione agli spostamenti dei pittori e dei vasai. Resta, tuttavia, da stabilire quali siano gli elementi che consentono di riconoscere questi spostamenti. Nel caso della ceramica della Magna Grecia, la mobilità umana rappresenta una chiave di lettura essenziale a causa dell’unità geografica del territorio, dell’interazione tra le colonie greche che si qualificano come centri di produzione e tra queste e la loro clientela (situata in prossimità o in centri posti a limitata distanza), della molteplicità dei centri di produzione e, infine, del fenomeno dello spostamento delle officine presso nuove committenze. Questo volume è dedicato a Enzo Lippolis che ha accompagnato e ispirato numerosi contributi qui pubblicati.Cette nouvelle série de recherches sur la céramique italiote a pour objectif de mettre à jour les connaissances sur cette production entrée dans l’ère du « post-Trendall », pour en faire un document susceptible d’éclairer l’histoire de la Grande Grèce aux époques classiques et hellénistiques. L’ouvrage affronte, à partir du cas de la Tombe 100 de Torre di Mare de Métaponte, le thème de la mobilité des peintres et de son rôle dans l’identité de la production. Ce phénomène n'est pas propre à la céramique italiote car le recentrage des études sur la question de la production a entraîné la mise en lumière des phénomènes qui président à la diffusion des techniques et des styles ou qui commandent la naissance et la fin des productions dans différentes régions du monde grec, à savoir, en premier lieu, les déplacements de peintres et de potiers. Il restait cependant à définir les différents indices permettant de les caractériser. Dans cas de la céramique de Grande Grèce, cette mobilité humaine représente une clef de lecture essentielle en raison de l’unité géographique du territoire, de l’interaction entre les colonies grecques productrices et leurs clientèles proches ou peu distantes et, enfin, de la multiplicité des centres de productions et du phénomène de dissémination des ateliers auprès des commanditaires. Ce volume est dédié à Enzo Lippolis, qui a accompagné et inspiré nombre des réflexions qui y sont présentées

Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome

BACKGROUND: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (<or=2.0 standard deviation score in 6 patients) significantly increased (P < 0.05) at the end of follow-up in comparison to values at diagnosis. Nonpostural persistent proteinuria was present in 6 patients, and 4 patients had a glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s). CONCLUSION: These data show that some patients with biallelic mutations in the chloride channel gene CLCNKB tend to present with pathological proteinuria and impaired kidney function after a median follow-up of 14 years, and growth retardation is common and sometimes related to growth hormone deficiency in these patients

Evaluation of commonly used ectoderm markers in iPSC trilineage differentiation.

Patient-derived induced pluripotent stem cells (iPSCs) have become a promising resource for exploring genetics of complex diseases, discovering new drugs, and advancing regenerative medicine. Increasingly, laboratories are creating their own banks of iPSCs derived from diverse donors. However, there are not yet standardized guidelines for qualifying these cell lines, i.e., distinguishing between bona fide human iPSCs, somatic cells, and imperfectly reprogrammed cells. Here, we report the establishment of a panel of 30 iPSCs from CD34+ peripheral blood mononuclear cells, of which 10 were further differentiated in vitro into all three germ layers. We characterized these different cell types with commonly used pluripotent and lineage specific markers, and showed that NES, TUBB3, and OTX2 cannot be reliably used as ectoderm differentiation markers. Our work highlights the importance of marker selection in iPSC authentication, and the need for the field to establish definitive standard assays

Lack of Association between Dialysis Modality and Outcomes in Atheroembolic Renal Disease

Background and objectives: Atheroembolic renal disease (AERD) can require dialytic support. Because anticoagulation may trigger atheroembolization, peritoneal dialysis may be preferred to hemodialysis. However, the effect of dialysis modality on renal and patient outcomes in AERD is unknown

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty.Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate).Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15-33.5) was available for 11. At first RTX administration, median creatinine and 24 -hour proteinuria were 1.17 mg/dl (IQR 0.83-1.62) and 5.2 g (IQR 3.3-8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16-52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45-46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immuno-suppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment.Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24 -hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for re-sponders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria

Clinical and laboratory findings in patients with Fabry disease.

<p>Clinical and laboratory findings in patients with Fabry disease.</p